Search Results (51)

The COVID-19 pandemic has revealed the profound and lasting impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the nervous system. Beyond acute infection, SARS-CoV-2 acts as a potent immunomodulatory agent, disrupting immune homeostasis and contributing to persistent inflammation, autoimmunity, and neurodegeneration. Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by a spectrum of neurological symptoms, including cognitive dysfunction, fatigue, neuropathy, and mood disturbances. These are linked to immune dysregulation involving cytokine imbalance, blood–brain barrier (BBB) disruption, glial activation, and T-cell exhaustion. Key biomarkers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NFL) correlate with disease severity and chronicity. This narrative review examines the immunopathological mechanisms underpinning the neurological sequelae of long COVID, focusing on neuroinflammation, endothelial dysfunction, and molecular mimicry. We also assess the role of viral variants in shaping neuroimmune outcomes and explore emerging diagnostic and therapeutic strategies, including biomarker-guided and immune-targeted interventions. By delineating how SARS-CoV-2 reshapes neuroimmune interactions, this review aims to support the development of precision-based diagnostics and targeted therapies for long COVID-related neurological dysfunction. Emerging approaches include immune-modulatory agents (e.g., anti-IL-6), neuroprotective drugs, and strategies for repurposing antiviral or anti-inflammatory compounds in neuro-COVID. Given the high prevalence of comorbidities, personalized therapies guided by biomarkers and patient-specific immune profiles may be essential. Advancements in vaccine technologies and targeted biologics may also hold promise for prevention and disease modification. Finally, continued interdisciplinary research is needed to clarify the complex virus–immune–brain axis in long COVID and inform effective clinical management. Full article

Nitazenes represent an emerging class of new synthetic opioids characterized by a high-potency μ-opioid receptor (MOR) agonist activity. Background: We report two 20-year-old males who presented with severe neurorespiratory depression with typical opioid syndrome, but no opioid identification based on routine blood and urine screening tests. The first patient recovered with supportive care, mechanical ventilation, and naloxone infusion, whereas the second patient developed post-anoxic cardiac arrest and died from brain death. Methods: A complementary comprehensive toxicological screening using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) was performed, and data were processed using a dedicated molecular network strategy to profile the metabolites. Results: Protonitazene and protonitazepyne, two nitazenes differing in their ethylamine moieties (i.e., a diethyl versus a pyrrolidine substitution, respectively), were identified. We found an extensive metabolism of protonitazene, leading to the identification of multiple phase I (resulting from hydroxylation, N-desethylation, and O-despropylation) and phase II (resulting from glucuronidation) metabolites. By contrast, protonitazepyne metabolism appeared limited, with one metabolite annotated confidently, protonitazepyne acid, which resulted from the oxidative pyrrolidine ring cleavage. Concusions: To conclude, nitazene detection is highly challenging due to its extensive structural and metabolic diversity. Our findings highlight the contribution of the untargeted LC-HRMS screening approach and suggest that diagnostic product ions can serve as robust markers for nitazene identification. Full article

Purpose: Post-COVID-19 syndrome (PCS) is characterized by low cardio-respiratory fitness (CRF). Recent research focuses on the role of autonomic nervous system dysfunction (AD) as a potential contributor to the diminished exercise performance. The aim is to determine the prevalence of AD—chronotropic insufficiency (CI) and abnormal heart rate recovery (HRR) in long-term PCS subjects and to analyse their association with exercise capacity. Patients and Methods: A total of 192 subjects with a history of SARS-CoV-2 infection were included. Chronic Fatigue Syndrome Questionnaire (CFSQ) was applied, and two symptomatic and asymptomatic emerged. Forty-seven had post-COVID complaints, persisting up to thirty months post-acute episode. CI and HRR were determined during the cardio-pulmonary exercise test (CPET). Results: Symptomatic subjects were divided into mild (20) and moderate-severe (27), depending on the CFSQ score; forty-eight PCS subjects without complaints served as a control group. Subjects with moderate-severe PCS showed lower peak VO2 (24.13 ± 6.1 mL/min/kg vs. 26.73 ± 5.9 mL/min/kg, vs. 27.01 ± 6.3 mL/min/kg), as compared to the mild/asymptomatic subjects. Diminished physical activity was established in 10 (37%) of the moderate-severe, 7 (35%) of the mildly symptomatic and 14 (29%) of the asymptomatic groups. The occurrence of AD in the mild/moderate-severe and control groups were, respectively, CI 35% vs. 81.5% vs. 12.5%. Abnormal HRR was, respectively, 20% vs. 33% vs. 8%. None of the subjects had depleted breathing reserve, dynamic hyperinflation, exercise bronchospasm or desaturation. Neither CI nor abnormal HRR correlated to peak O2. Conclusions: AD is present among long-term PCS subjects and may limit the cardio-respiratory response to exercise but is not independently associated with it. Assuming the multiorgan ANS innervation, it is highly probable that AD has diverse pathological pathways in the various PCS phenotypes and contributes differently by cerebral, cardiovascular, respiratory, peripheral or mixed pathways to the diminished neuro-cognitive and physical performance. Full article

Introduction: Comorbidities affect diagnosis and treatments in cancer patients. This study explores the prevalence and patterns of comorbidities in non-small cell lung cancer (NSCLC) patients and their association with survival. Materials and Methods: This retrospective population-based cohort study included 1674 incident NSCLC patients. Comorbidities were classified based on the ICD-9-CM system, with 13 disease categories analyzed. Patients with more than two comorbidities were classified into three mutually exclusive and exhaustive latent classes (Latent Class Analysis [LCA]). The optimal number of latent classes was determined by applying the Akaike Information Criterion. Cox regression models were run to assess overall and cancer-specific mortality, adjusting for the comorbidity groups, sex, age, and stage at diagnosis. Results: In 1674 NSCLC patients, the most prevalent medical conditions were respiratory (35.8%) and cardiovascular (33.5%). The Cox regression showed that even one comorbidity is associated with an increased hazard of overall mortality (HR = 1.33, 95%CI: 1.11–1.59, p = 0.002). LCA-derived Class-1 (cardiovascular-respiratory and endocrine) reported HR = 1.74 (95%CI: 1.39–2.17, p < 0.001), Class-2 (multi-organ) HR = 1.44 (95%CI: 1.18–1.77, p < 0.001), and Class-3 (socio-multifactorial-neuro) HR = 1.62 (95%CI: 1.36–1.93, p < 0.001). Instead, in patients with one comorbidity, NSCLC-specific mortality showed no significant trend towards increased risk (HR = 1.17, 95%CI: 1.00–1.43, p = 0.114). Significant associations emerged between NSCLC-specific mortality and LCA-classes: Class-1: HR = 1.49 (95%CI: 1.20–1.91, p = 0.001); Class-2 HR = 1.25 (95%CI: 1.0–1.57 p = 0.048); and Class-3: HR = 1.23 (95%CI: 1.00–1.48, p = 0.035). Conclusions: The adverse impact of comorbidities on NSCLC-specific mortality requires their inclusion as risk factors in cancer treatment and prognosis. Full article

Background/Objectives: Sleep-disordered breathing (SDB) is a primary concern in children’s health. Research suggests that repeated oxygen drops during sleep—common in SDB—may harm the brainstem’s breathing control centres. This damage likely occurs through oxidative stress, inflammation, and cell death, which weaken the brain’s ability to regulate breathing. Over time, these effects could lead to functional changes (e.g., disrupted chemical signalling) and physical damage in critical brain regions, creating a cycle of unstable breathing. However, much of this evidence comes from animal or lab studies, leaving gaps in our understanding of how these mechanisms work in humans. This review synthesises existing research on how breathing disruptions during sleep—particularly episodes of intermittent hypoxia—affect the brain’s ability to control respiration in children and adolescents. Methods: We analysed studies from medical databases PubMed, Scopus, and Web of Science, focusing on how SDB (obstructive or central sleep apnoea) impacts the brain’s respiratory centres in young populations. Animal studies and research involving children on mechanical ventilation were excluded to focus on natural sleep patterns. Results: After removing duplicates, 54 studies remained. Additionally, 43 record were excluded for various reasons. Ultimately, 11 articles were selected for the final analysis, including three that focused on genetic conditions, such as Down syndrome, Prader–Willi syndrome, and Pierre Robin sequence. The findings suggest that repeated oxygen dips during sleep may harm the brainstem’s respiratory control areas, especially during critical developmental stages. This damage could lead to long-term issues, such as unstable breathing, cardiovascular strain, or neurological problems. However, most studies only captured the immediate effects of low oxygen, leaving uncertainty about permanent harm due to a lack of long-term follow-up. Conclusions: Repeated oxygen deprivation during sleep appears to damage the brainstem and disrupt breathing regulation. However, small study sizes and short observation periods limit the strength of these conclusions. Future research should use advanced imaging tools to clarify long-term risks, develop effective treatments, and track children over extended periods. More significantly, longer-term studies are urgently needed to guide clinical care for vulnerable populations. Full article

Background and Objectives: Data regarding long-term outcomes of gastrostomy-fed children is scarce. The aim of the study was to analyze the long-term follow-up of children receiving percutaneous endoscopic gastrostomy (PEG) in terms of nutritional outcomes, hospitalization, and fundoplication rates. Materials and Methods: The medical records of gastrostomy-fed children who underwent PEG placement between January 2002 and June 2022 and subsequently attended primary care clinics of the Clalit Health Services (CHS) in Northeastern Israel, were reviewed in this retrospective cohort study. Results: A total of 372 gastrostomy tubes (GT) were placed, 88% of the children had neuro-developmental impairment. During the median follow-up of 64 months, 230 patients (62%) had frequent recurrent hospitalizations defined as at least two hospitalizations per year on average. Hospitalizations were due to respiratory infections in 52%. Among 322 patients who underwent iron status work-up, (64%) and (31%) had iron deficiency (ID) and ID anemia, respectively. Laboratory monitoring of other micronutrient levels was limited but showed that 25/73 (34%) had vitamin D deficiencies, without significant association with recurrent hospitalization (p > 0.1). A total of 12% of the patients underwent subsequent fundoplication. Conclusions: This study confirmed the durability of gastrostomy tube feeding in children with neurological impairment, noting a low prevalence of fundoplication but a high rate of hospitalizations, primarily due to respiratory infections. Regular assessment of micronutrient deficiencies, particularly vitamin D, is recommended for these patients. Full article

Coronavirus disease 2019 (COVID-19) has been a global pandemic affecting millions of people’s lives, which has led to ‘post-COVID-19 fatigue’. Alarmingly, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) not only infects the lungs but also influences the heart and brain. Endothelial cell dysfunction and hypercoagulation, which we know occur with this infection, lead to thrombo-inflammation that can manifest as many myriad cardio-cerebrovascular disorders, such as brain fog, fatigue, cognitive dysfunction, etc. Additionally, SARS-CoV-2 has been associated with oxidative stress, protein aggregation, cytokine storm, and mitochondrial dysfunction in neurodegenerative diseases. Accordingly, the identification of molecular targets involved in these actions could provide strategies for preventing and treating this disease. In particular, the very common enzyme dipeptidyl peptidase IV (DPPIV) has recently been identified as a candidate co-receptor for the cell entry of the SARS-CoV-2 virus with its involvement in infection. In addition, DPPIV has been reported as a co-receptor for some viruses such as Middle East respiratory syndrome-coronavirus (MERS-CoV). It mediates immunologic reactions and diseases such as type 2 diabetes mellitus, obesity, and hypertension, which have been considered the prime risk factors for stroke among other types of cardio-cerebrovascular diseases. Unlike angiotensin-converting enzyme 2 (ACE2), DPPIV has been implicated in aggravating the course of infection due to its disruptive effect on inflammatory signaling networks and the neuro–glia–vascular unit. Regarding the neurological, physiological, and molecular grounds governing post-COVID-19 fatigue, this review focuses on DPPIV as one of such reasons that progressively establishes cerebrovascular grievances following SARS-CoV infection. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19), induced a global pandemic with a diverse array of clinical manifestations. While the acute phase of the pandemic may be waning, the intricacies of COVID-19′s impact on neurological health remain a crucial area of investigation. Early recognition of the spectrum of COVID-19 symptoms, ranging from mild fever and cough to life-threatening respiratory distress and multi-organ failure, underscored the significance of neurological complications, including anosmia, seizures, stroke, disorientation, encephalopathy, and paralysis. Notably, patients requiring intensive care unit (ICU) admission due to neurological challenges or due to them exhibiting neurological abnormalities in the ICU have shown increased mortality rates. COVID-19 can lead to a range of neurological complications such as anosmia, stroke, paralysis, cranial nerve deficits, encephalopathy, delirium, meningitis, seizures, etc., in affected patients. This review elucidates the burgeoning landscape of neurological sequelae associated with SARS-CoV-2 infection and explores the underlying neurobiological mechanisms driving these diverse manifestations. A meticulous examination of potential neuroinvasion routes by SARS-CoV-2 underscores the intricate interplay between the virus and the nervous system. Moreover, we dissect the diverse neurological manifestations emphasizing the necessity of a multifaceted approach to understanding the disease’s neurological footprint. In addition to elucidating the pathophysiological underpinnings, this review surveys current therapeutic modalities and delineates prospective avenues for neuro-COVID research. By integrating epidemiological, clinical, and diagnostic parameters, we endeavor to foster a comprehensive analysis of the nexus between COVID-19 and neurological health, thereby laying the groundwork for targeted therapeutic interventions and long-term management strategies. Full article

This review delves into the complex relationship between environmental factors, their mechanistic cellular and molecular effects, and their significant impact on human health. Climate change is fueled by industrialization and the emission of greenhouse gases and leads to a range of effects, such as the redistribution of disease vectors, higher risks of disease transmission, and shifts in disease patterns. Rising temperatures pose risks to both food supplies and respiratory health. The hypothesis addressed is that environmental stressors including a spectrum of chemical and pathogen exposures as well as physical and psychological influences collectively impact genetics, metabolism, and cellular functions affecting physical and mental health. The objective is to report the mechanistic associations linking environment and health. As environmental stressors intensify, a surge in health conditions, spanning from allergies to neurodegenerative diseases, becomes evident; however, linkage to genetic-altered proteomics is more hidden. Investigations positing that environmental stressors cause mitochondrial dysfunction, metabolic syndrome, and oxidative stress, which affect missense variants and neuro- and immuno-disorders, are reported. These disruptions to homeostasis with dyslipidemia and misfolded and aggregated proteins increase susceptibility to cancers, infections, and autoimmune diseases. Proposed interventions, such as vitamin B supplements and antioxidants, target oxidative stress and may aid mitochondrial respiration and immune balance. The mechanistic interconnections of environmental stressors and disruptions in health need to be unraveled to develop strategies to protect public health. Full article

A growing body of evidence indicates that a neuropathological cross-talk takes place between the coronavirus disease 2019 (COVID-19) -the pandemic severe pneumonia that has had a tremendous impact on the global economy and health since three years after its outbreak in December 2019- and Alzheimer’s Disease (AD), the leading cause of dementia among human beings, reaching 139 million by the year 2050. Even though COVID-19 is a primary respiratory disease, its causative agent, the so-called Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), is also endowed with high neuro-invasive potential (Neurocovid). The neurological complications of COVID-19, resulting from the direct viral entry into the Central Nervous System (CNS) and/or indirect systemic inflammation and dysregulated activation of immune response, encompass memory decline and anosmia which are typically associated with AD symptomatology. In addition, patients diagnosed with AD are more vulnerable to SARS-CoV-2 infection and are inclined to more severe clinical outcomes. In the present review, we better elucidate the intimate connection between COVID-19 and AD by summarizing the involved risk factors/targets and the underlying biological mechanisms shared by these two disorders with a particular focus on the Angiotensin-Converting Enzyme 2 (ACE2) receptor, APOlipoprotein E (APOE), aging, neuroinflammation and cellular pathways associated with the Amyloid Precursor Protein (APP)/Amyloid beta (Aβ) and tau neuropathologies. Finally, the involvement of ophthalmological manifestations, including vitreo-retinal abnormalities and visual deficits, in both COVID-19 and AD are also discussed. Understanding the common physiopathological aspects linking COVID-19 and AD will pave the way to novel management and diagnostic/therapeutic approaches to cope with them in the post-pandemic future. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded RNA virus and a member of the corona virus family, primarily affecting the upper respiratory system and the lungs. Like many other respiratory viruses, SARS-CoV-2 can spread to other organ systems. Apart from causing diarrhea, another very common but debilitating complication caused by SARS-CoV-2 is neurological symptoms and cognitive difficulties, which occur in up to two thirds of hospitalized COVID-19 patients and range from shortness of concentration and overall declined cognitive speed to executive or memory function impairment. Neuro-cognitive dysfunction and “brain fog” are frequently present in COVID-19 cases, which can last several months after the infection, leading to disruption of daily life. Cumulative evidence suggests that SARS-CoV-2 affects vasculature in the extra-pulmonary systems directly or indirectly, leading to impairment of endothelial function and even multi-organ damage. The post COVID-19 long-lasting neurocognitive impairments have not been studied fully and their underlying mechanism remains elusive. In this review, we summarize the current understanding of the effects of COVID-19 on vascular dysfunction and how vascular dysfunction leads to cognitive impairment in patients. Full article

The COVID-19 sequelae have been shown to affect respiratory and cardiological functions as well as neuro-psychological functions, and, in some cases, metabolic/nutritional aspects. The Italian National Institute for Insurance against Accidents at Work (Istituto Nazionale Assicurazione Infortuni sul Lavoro, INAIL) recorded that, until December 2022, 315,055 workers were affected by COVID-19; therefore, there is a need to identify an effective approach to treat such patients. Robotic and technological devices could be integrated into the rehabilitation programme of people with long COVID conditions. A review of the literature showed that telerehabilitation may improve functional capacity, dyspnoea, performance, and quality of life in these patients, but no studies were found evaluating the effects of robot-mediated therapy or virtual reality systems. Considering the above, Fondazione Don Carlo Gnocchi and INAIL propose a multi-axial rehabilitation for workers with COVID-19 sequelae. To accomplish this goal, the two institutions merged the epidemiological information gathered by INAIL, the expertise in robotic and technological rehabilitation of Fondazione Don Carlo Gnocchi, and the literature review. Our proposal aims to facilitate a multi-axial rehabilitation approach customized to meet the unique needs of each individual, with a particular emphasis on utilizing advanced technologies to address the current and future challenges of patient care. Full article

Sleep is a fundamental biological necessity, the lack of which has severe repercussions on the mental and physical well-being in individuals of all ages. The phrase “sleep-disordered breathing (SDB)” indicates a wide array of conditions characterized by snoring and/or respiratory distress due to increased upper airway resistance and pharyngeal collapsibility; these range from primary snoring to obstructive sleep apnea (OSA) and occur in all age groups. In the general pediatric population, the prevalence of OSA varies between 2% and 5%, but in some particular clinical conditions, it can be much higher. While adenotonsillar hypertrophy (“classic phenotype”) is the main cause of OSA in preschool age (3–5 years), obesity (“adult phenotype”) is the most common cause in adolescence. There is also a “congenital–structural” phenotype that is characterized by a high prevalence of OSA, appearing from the earliest ages of life, supported by morpho-structural abnormalities or craniofacial changes and associated with genetic syndromes such as Pierre Robin syndrome, Prader-Willi, achondroplasia, and Down syndrome. Neuromuscular disorders and lysosomal storage disorders are also frequently accompanied by a high prevalence of OSA in all life ages. Early recognition and proper treatment are crucial to avoid major neuro-cognitive, cardiovascular, and metabolic morbidities. Full article

With the routine use of effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, the number of life-threatening coronavirus disease 2019 (COVID-19) courses have largely been reduced. However, multiple COVID-19 convalescents, even after asymptomatic to moderate disease, suffer from post-COVID syndrome, with relevant limitations in daily life. The pathophysiologic mechanisms of post-COVID syndrome are still elusive, with dysregulation of the immune system suggested as a central mechanism. Here, we assessed COVID-19 post-infectious symptoms (5–6 months after PCR-confirmed acute infection) together with the humoral immune response against SARS-CoV-2 in non-hospitalized COVID-19 convalescents, early (5–6 weeks) and late (5–6 months) after their first positive SARS-CoV-2 PCR result. Convalescents reporting several post-infectious symptoms (>3) showed higher anti-spike and anti-nucleocapsid antibody levels 5–6 weeks after PCR-confirmed infection with the latter remained increased 5–6 months after positive PCR. Likewise, a higher post-infectious symptom score was associated with increased antibody levels. Of note, convalescents displaying neuro-psychiatric symptoms such as restlessness, palpitations, irritability, and headache, as well as general symptoms such as fatigue/reduced power had higher SARS-CoV-2-specific antibody levels compared with asymptomatic cases. The increased humoral immune response in convalescents with post-COVID syndrome might be useful for the detection of individuals with an increased risk for post-COVID syndrome. Full article

Background: The Coronavirus Disease 2019 (COVID-19) is a global pandemic that has killed over 1.5 million people worldwide. A constellation of multisystem involvement with SARS-CoV-2 has been reported. COVID-19 has been shown to affect the human nervous system, however, both the extent and severity of involvement have yet to be fully elucidated. In this manuscript, we aimed to better understand the effect of COVID-19 on neuro-respiratory status by studying COVID-19 patients who presented with central apnea. Methodology: We analyzed patient characteristics, clinical outcomes, laboratory results, and imaging results of three patients with symptomatic, PCR-proven COVID-19 and episodes of central apnea. Results: Of the three patients included in this study, two patients developed new central apnea, and one patient developed an exacerbation of underlying central apnea despite COVID-19 treatments with systemic steroids and remdesivir. All occurred, on average, 15 days after the onset of COVID-19 symptoms. At 1-year follow-up, all patients experienced complete resolution of apneic breathing. Conclusions: Physicians should be vigilant for the presentation of COVID-19 with central apnea. Central apnea may be a complication in patients with severe COVID-19 infection. More research is warranted to further understand this association. Full article